scholarly journals Candesartan Cilexetil Improves Angiotensin II Type 2 Receptor-Mediated Neurite Outgrowth via the PI3K-Akt Pathway in Fructose-Induced Insulin-Resistant Rats

Diabetes ◽  
2012 ◽  
Vol 61 (4) ◽  
pp. 925-932 ◽  
Author(s):  
N. Hashikawa-Hobara ◽  
N. Hashikawa ◽  
Y. Inoue ◽  
H. Sanda ◽  
Y. Zamami ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Neurite Outgrowth ◽  
Candesartan Cilexetil ◽  
Akt Pathway ◽  
Insulin Resistant

scholarly journals Involvement of Protein Kinase Cα (PKCα) in the Early Action of Angiotensin II Type 2 (AT2) Effects on Neurite Outgrowth in NG108–15 Cells: AT2-Receptor Inhibits PKCα and p21ras Activity

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4263-4272 ◽  
Author(s):  
Hélène Beaudry ◽  
Louis Gendron ◽  
Marie-Odile Guimond ◽  
Marcel D. Payet ◽  
Nicole Gallo-Payet
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinase ◽  
Neurite Outgrowth ◽  
At2 Receptor ◽  
Early Action ◽  
Protein Kinase Cα

scholarly journals Direct Stimulation of Angiotensin II Type 2 Receptor Enhances Spatial Memory

2011 ◽  
Vol 32 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Fei Jing ◽  
Masaki Mogi ◽  
Akiko Sakata ◽  
Jun Iwanami ◽  
Kana Tsukuda ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Angiotensin Ii ◽  
Neurite Outgrowth ◽  
Hippocampal Neurons ◽  
Receptor Agonist ◽  
Laser Speckle ◽  
Morris Water Maze Test ◽  
Direct Stimulation ◽  
Stimulation Of

We examined the possibility that direct stimulation of the angiotensin II type 2 (AT2) receptor by a newly generated direct AT2 receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT2 receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B2 receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT2 receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-β (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT2 receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.

scholarly journals Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes: an IMI-RHAPSODY Study

2021 ◽  
Author(s):  
Roderick C Slieker ◽  
Louise A Donnelly ◽  
Hugo Fitipaldi ◽  
Gerard A Bouland ◽  
Giuseppe N. Giordano ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Molecular Signature ◽  
Akt Pathway ◽  
Molecular Profile ◽  
Molecular Signatures ◽  
Insulin Resistant ◽  
Protein Levels ◽  
Mild Diabetes

Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease

scholarly journals Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes: an IMI-RHAPSODY Study

2021 ◽  
Author(s):  
Roderick C Slieker ◽  
Louise A Donnelly ◽  
Hugo Fitipaldi ◽  
Gerard A Bouland ◽  
Giuseppe N. Giordano ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Molecular Signature ◽  
Akt Pathway ◽  
Molecular Profile ◽  
Molecular Signatures ◽  
Insulin Resistant ◽  
Protein Levels ◽  
Mild Diabetes

Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease

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